The epithelial-mesenchymal transition (EMT) is crucial to cancer progression and metastasis. Although multiple cellular miRNAs have been identified to regulate the EMT and metastasis in cancers, the ...role of viral miRNAs in cancer progression remains largely unknown. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy typically characterized by its early metastasis. In the present study, we have discovered the involvement of a viral miRNA, EBV-miR-BART7-3p, in the EMT and metastasis of NPC cells. Initially, we observed that EBV-miR-BART7-3p was highly expressed in NPC and positively correlated with lymph node metastasis and clinical stage of NPC. Subsequently, we demonstrated that EBV-miR-BART7-3p enhanced cell migration/invasion in vitro, cancer metastasis in vivo, and particularly the EMT characterized by loss of epithelial markers and gain of mesenchymal features in NPC cells. Furthermore, mechanistic studies disclosed that EBV-miR-BART7-3p targeted a major human tumor suppressor PTEN, modulating PI3K/Akt/GSK-3β signaling and eventually leading to the high expression and nuclear accumulation of Snail and β-catenin, which favor EMT. Knockdown of PTEN could phenocopy the effect of EBV-miR-BART7-3p, whereas re-expression of PTEN resulted in a phenotypic reversion. Moreover, these findings were supported by an observation of an EBV-positive cell model in which silencing of endogenous EBV-miR-BART7-3p partially attenuated cell migration/invasion and altered EMT protein expression pattern via reverting PI3K/Akt, Snail and β-catenin expression. Thus, this study suggests a novel mechanism by which EBV-miR-BART7-3p modulates the EMT and metastasis of NPC cells, and a clinical implication of EBV-miR-BART7-3p as a potential biomarker or therapeutic target.
Driven by increasingly stringent restrictions on long-chain per- and polyfluoroalkyl substances (PFASs), novel fluorinated compounds have emerged on the market. Here we report on the occurrences of ...several perfluoroalkyl ether carboxylic and sulfonic acids (PFECAs and PFESAs), including hexafluoropropylene oxide dimer and trimer acids (HFPO-DA and HFPO-TA), ammonium 4,8-dioxa-3H-perfluorononanoate (ADONA), chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFESA), and its hydrogen-substituted analogue (6:2 H-PFESA) in surface waters from China (n = 106), the United States (n = 12), the United Kingdom (n = 6), Sweden (n = 10), Germany (n = 14), The Netherlands (n = 6), and Korea (n = 6). Results showed that HFPO-DA, HFPO-TA, and 6:2 Cl-PFESA (median = 0.95, 0.21, and 0.31 ng/L, respectively) were frequently detected in all countries, indicating ubiquitous dispersal and distribution in global surface waters. The presence of 6:2 H-PFESA was widely detected in China (detection rate > 95%) but not in any other country. Only trace levels of ADONA (0.013–1.5 ng/L) were detected in the Rhine River flowing through Germany. The estimated total riverine mass discharges of HFPO-DA, HFPO-TA, and ΣPFESAs reached 2.6, 6.0, and 4.3 ton/year in five of the major river systems in China. Our results indicated that novel PFECAs and PFESAs might become global contaminants, and future investigations are warranted.
We report on the highest energy photons from the Crab Nebula observed by the Tibet air shower array with the underground water-Cherenkov-type muon detector array. Based on the criterion of a muon ...number measured in an air shower, we successfully suppress 99.92% of the cosmic-ray background events with energies E>100 TeV. As a result, we observed 24 photonlike events with E>100 TeV against 5.5 background events, which corresponds to a 5.6σ statistical significance. This is the first detection of photons with E>100 TeV from an astrophysical source.
An overview of Sun–Sky Radiometer Observation Network (SONET) measurements in China is presented. Based on observations at 16 distributed SONET sites in China, atmospheric aerosol parameters are ...acquired via standardization processes of operational measurement, maintenance, calibration, inversion, and quality control implemented since 2010. A climatology study is performed focusing on total columnar atmospheric aerosol characteristics, including optical (aerosol optical depth, ÅngstrÖm exponent, fine-mode fraction, single-scattering albedo), physical (volume particle size distribution), chemical composition (black carbon; brown carbon; fine-mode scattering component, coarse-mode component; and aerosol water), and radiative properties (aerosol radiative forcing and efficiency). Data analyses show that aerosol optical depth is low in the west but high in the east of China. Aerosol composition also shows significant spatial and temporal variations, leading to noticeable diversities in optical and physical property patterns. In west and north China, aerosols are generally affected by dust particles, while monsoon climate and human activities impose remarkable influences on aerosols in east and south China. Aerosols in China exhibit strong light-scattering capability and result in significant radiative cooling effects.
We revisit the diagonal ridge feature (diagonal distributions in the R, vφ plane) found in Gaia and present a timing analysis for it between Galactocentric distances of R = 7.5 and 12 kpc, using ...main-sequence turnoff and OB stars selected from the LAMOST Galactic spectroscopic surveys. We recover the ridge pattern in the R-vφ plane color coded by mean radial velocity and find that this feature is presented from very young (OB stars, few hundred megayears) to very old populations (τ = 9-14 Gyr). Meanwhile, some ridge features are also revealed in the metallicity Fe/H, /Fe, and vz distributions. In the LZ, vφ plane, one of the ridge patterns, with constant angular momentum per unit mass, shows variations with different age populations compared. However, the remaining two are relatively stable, implying there might be two kinds of ridge patterns with different dynamical origins and evolutions.
We report, for the first time, the long-awaited detection of diffuse gamma rays with energies between 100 TeV and 1 PeV in the Galactic disk. Particularly, all gamma rays above 398 TeV are observed ...apart from known TeV gamma-ray sources and compatible with expectations from the hadronic emission scenario in which gamma rays originate from the decay of π^{0}'s produced through the interaction of protons with the interstellar medium in the Galaxy. This is strong evidence that cosmic rays are accelerated beyond PeV energies in our Galaxy and spread over the Galactic disk.
•l-his and l-lys cause the transformation of secondary structures of porcine myosin.•R-SH and hydrophobic groups are exposed in the presence of l-his and l-lys.•l-his and l-lys increase the ...solubility of porcine myosin at all ionic strengths.•l-lys contributes more to solubility than l-his due to more loss of α-helix.
The influence of l-lys and l-his on the solubility, surface hydrophobicity, sulphydryl content and conformational characteristics of porcine myosin solubilised in high (0.6M), physiological (0.15M) and low (1mM) ionic strength solutions were explored. The solubility of myosin was increased in the presence of l-his and/or l-lys in all ionic strength solutions used. The presence of l-his and l-lys caused increases in the surface hydrophobicity and reactive sulphydryl content (p<0.05). Circular dichroism revealed a significant decrease of α-helical content with an increase of random coils, β-turns and β-sheets in the presence of l-his and/or l-lys. These results demonstrate that the introduction of l-lys and l-his causes the unfolding of myosin, resulting in loss of α-helical structure, which is followed by increases in random coils, β-turns and β-sheets, which exposes buried hydrophobic and sulphydryl groups to the myosin surface, ultimately increasing the solubility of porcine myosin.
Here, we report on the occurrence of a novel perfluoroalkyl ether carboxylic acid, ammonium perfluoro-2-(propoxy)propoxy-1-propanoate (HFPO-TA), in surface water and common carp (Cyprinus carpio) ...collected from the Xiaoqing River and in residents residing near a fluoropolymer production plant in Huantai County, China. Compared with the levels upstream of the Xiaoqing River, HFPO-TA concentrations (5200–68500 ng/L) were approximately 120–1600-times higher downstream after receiving fluoropolymer plant effluent from a tributary. The riverine discharge of HFPO-TA was estimated to be 4.6 t/yr, accounting for 22% of total PFAS discharge. In the wild common carp collected downstream from the point source, HFPO-TA was detected in the blood (median: 1510 ng/mL), liver (587 ng/g ww), and muscle (118 ng/g ww). The log BCFblood of HFPO-TA (2.18) was significantly higher than that of PFOA (1.93). Detectable levels of HFPO-TA were also found in the sera of residents (median: 2.93 ng/mL). This is the first report on the environmental occurrence and bioaccumulation of this novel chemical. Our results indicate an emerging usage of HFPO-TA in the fluoropolymer manufacturing industry and raise concerns about the toxicity and potential health risks of HFPO-TA to aquatic organisms and humans.
•To-bus accessibility and by-bus accessibility significantly affect housing prices in the bus-dependent city.•Spatial heterogeneity exists in the price effects of bus accessibility.•Bus frequency ...exerts a larger price effect in the peripheral area than in the central.
Accessibility to transit facilities is perceived to affect property prices. However, accessibility by transit has rarely elicited adequate scholarly attention in property price analyses. Additionally, previous studies on how transit accessibility affects property prices mainly focused on rail and bus rapid transit systems, while conventional bus transit, which is very popular in many contexts, has seldom been investigated. Moreover, whether there is spatial heterogeneity in the price (or capitalization) effects of conventional bus accessibility remains to be explored. To fill these gaps, this study aims to investigate the role of accessibility to and by bus in determining housing prices in a bus-dependent city where urban transit service is offered mainly by a bus system rather than other transit systems. Using a database of 4966 condominium units in Xiamen, China, this study develops a battery of spatial econometric models to estimate global and local relationships between to-bus and by-bus accessibility and housing prices. The findings are as below: (1) to-bus accessibility (measured by the number of nearby bus stops) is positively associated with nearby housing prices; (2) by-bus accessibility (measured by travel time to city centers by bus and bus frequency) significantly affects nearby housing prices; (3) spatial heterogeneity exists in the price effects of bus accessibility; and (4) bus frequency exerts a larger price effect in the peripheral area than in the central. Finally, practical and policy implications are discussed.
To elucidate the cytotoxicity mechanism of Garnoderma triterpenes, a chemoproteomic study using five purified ganoderic acids, ganoderic acid F (GAF), ganoderic acid K (GAK), ganoderic B (GAB), ...ganoderic acid D (GAD) and ganoderic acid AM1 (GAAM1) was conducted. GAF, GAK, GAB, GAD and GAAM1 treatment for 48 h inhibited the proliferation of HeLa human cervical carcinoma cells with IC
50 values of 19.5±0.6
μM, 15.1±0.5
μM, 20.3±0.4
μM, 17.3±0.3
μM, 19.8±0.7
μM, respectively. The protein expression profiles of HeLa cells treated with each ganoderic acid at dose of 15
μM for 48
h were checked using two-dimensional electrophoresis (2-DE). The possible target-related proteins of ganoderic acids, i.e. proteins with same change tendency in all five ganoderic acids-treated groups compared with control, were identified using MALDI-TOF MS/MS. Twelve proteins including human interleukin-17E, eukaryotic translation initiation factor 5A (eIF5A), peroxiredoxin 2, ubiquilin 2, Cu/Zn-superoxide dismutase, 14-3-3 beta/alpha, TPM4-ALK fusion oncoprotein type 2, PP2A subunit A PR65-alpha isoform, nucleobindin-1, heterogeneous nuclear ribonucleoprotein K, reticulocalbin 1 and chain A of DJ-1 protein were identified. Ganoderic acids might exert their cytotoxicity by altering proteins involved in cell proliferation and/or cell death, carcinogenosis, oxidative stress, calcium signaling and ER stress.
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